The analysis of polymeric excipients using ultra-high-performance supercritical fluid chromatography and mass spectrometry
The analysis of polymeric excipients using ultra-high-performance supercritical fluid chromatography and mass spectrometry
Even though the approval of small molecules is still of great importance, the expansion towards newer modalities requires the development of druggable large biomolecules with inherent challenges in their delivery due to their toxicity, poor bioavailability, or lack of cell specificity. The result is that drugs are being formulated in complex drug-excipient conjugates to address the emerging challenges in drug delivery. Polymers are popular excipients due to their synthetic versatility, allowing for achieving the desired pharmacological and physicochemical characteristics of the final product. The use of poly(ethylene) glycols or cyclodextrins as excipients in some formulations enables the production of robust formulations. Poly(ethylene) glycols are safe materials that improve drug delivery by drug encapsulation or binding. Cyclodextrins host drug molecules in their cavity to improve their solubility.
The polymeric nature of the materials requires control of their quality from the early stages of drug development. The synthetic approaches of poly(ethylene) glycols as the raw material and the possible degradation pathways lead to the formation of undesired subproducts. The synthesis of (2-hydroxypropyl) cyclodextrin produces a complex mixture that is difficult to characterise. The resulting heterogeneity can lead to sub-potency, so the dose is not administered as required, compromising the treatment reaching the patient. These findings showed the need for further characterisation of the excipients used.
This research proposes the combination of ultra-high-performance supercritical fluid chromatography and mass spectrometry to characterise and quantify polymeric excipients, specifically poly(ethylene) glycols and (2-hydroxypropyl) cyclodextrin. The aim was to facilitate the characterisation and quantitation of the materials.
SFC, pharmaceutical, Mass Spectrometry, Chromatography, Polymer, PEG, Cyclodextrin, Supercritical fluid chromatography, Drug delivery
University of Southampton
Cancho Gonzalez, Sergio
1fc211b0-5c0f-4435-8935-51eef7f2f212
6 January 2023
Cancho Gonzalez, Sergio
1fc211b0-5c0f-4435-8935-51eef7f2f212
Baud, Matthias
8752d519-3d33-43b6-9a77-ab731d410c2e
Langley, Graham
7ac80d61-b91d-4261-ad17-255f94ea21ea
Herniman, Julie
530b1a36-1386-4602-8df7-defa6eb3512b
Cancho Gonzalez, Sergio
(2023)
The analysis of polymeric excipients using ultra-high-performance supercritical fluid chromatography and mass spectrometry.
University of Southampton, Doctoral Thesis, 367pp.
Record type:
Thesis
(Doctoral)
Abstract
Even though the approval of small molecules is still of great importance, the expansion towards newer modalities requires the development of druggable large biomolecules with inherent challenges in their delivery due to their toxicity, poor bioavailability, or lack of cell specificity. The result is that drugs are being formulated in complex drug-excipient conjugates to address the emerging challenges in drug delivery. Polymers are popular excipients due to their synthetic versatility, allowing for achieving the desired pharmacological and physicochemical characteristics of the final product. The use of poly(ethylene) glycols or cyclodextrins as excipients in some formulations enables the production of robust formulations. Poly(ethylene) glycols are safe materials that improve drug delivery by drug encapsulation or binding. Cyclodextrins host drug molecules in their cavity to improve their solubility.
The polymeric nature of the materials requires control of their quality from the early stages of drug development. The synthetic approaches of poly(ethylene) glycols as the raw material and the possible degradation pathways lead to the formation of undesired subproducts. The synthesis of (2-hydroxypropyl) cyclodextrin produces a complex mixture that is difficult to characterise. The resulting heterogeneity can lead to sub-potency, so the dose is not administered as required, compromising the treatment reaching the patient. These findings showed the need for further characterisation of the excipients used.
This research proposes the combination of ultra-high-performance supercritical fluid chromatography and mass spectrometry to characterise and quantify polymeric excipients, specifically poly(ethylene) glycols and (2-hydroxypropyl) cyclodextrin. The aim was to facilitate the characterisation and quantitation of the materials.
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Submitted date: 1 June 2022
Published date: 6 January 2023
Keywords:
SFC, pharmaceutical, Mass Spectrometry, Chromatography, Polymer, PEG, Cyclodextrin, Supercritical fluid chromatography, Drug delivery
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Local EPrints ID: 474911
URI: http://eprints.soton.ac.uk/id/eprint/474911
PURE UUID: 37359c9f-a89d-4a91-b579-82bccaa07361
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Date deposited: 07 Mar 2023 17:30
Last modified: 10 Apr 2024 04:01
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Author:
Sergio Cancho Gonzalez
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